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Academician forum
Facing the trends of “Double First-Class” initiative, enhancing the construction of top disciplines: some thoughts on the construction of oral and maxillofacial surgery in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
QIU Weiliu
2022, 42 (9):  1163-1170. 
doi: 10.3969/j.issn.1674-8115.2022.09.001

Abstract ( 59 )   HTML ( 187 )   PDF (7021KB) ( 82 )  

The core of “Double First-Class” initiative is discipline construction. Through reviewing the development and the achievements of the Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, and two guiding thoughts, i.e., “high ambition” and “reform and opening up”, the following four experiences are summarized: talent cultivation and echelon construction, talent diversion to increase spillover effect, advocating interdisciplinarity and transdisciplinarity, and introducing system reform and discipline innovation. Furthermore, four suggestions for the future are proposed: the oral and maxillofacial surgery of “Chinese style” should be changed to “Chinese characteristics”; innovation should be taken as the forerunner and scientific research as the soul; with the integration of natural science and humanities as the breakthrough point and the guidance of integration, the interdisciplinary talents should be trained; humanistic education in medicine should be further enhanced.

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New progress and prospects of blood glucose monitoring technology
JIA Weiping
2022, 42 (9):  1171-1175. 
doi: 10.3969/j.issn.1674-8115.2022.09.002

Abstract ( 60 )   HTML ( 182 )   PDF (1658KB) ( 82 )  

Glucose monitoring is an important part of diabetes management. For over a century, diabetes monitoring technology has developed from the initial urine glucose test, to the later blood glucose test, and finally to the current continuous glucose monitoring (CGM), which is evolving in a more convenient, accurate, minimally invasive, and even non-invasive direction. CGM refers to the technology that continuously measures glucose concentrations in the subcutaneous interstitial fluid by glucose sensors. It can detect hyperglycemia and hypoglycemia that are not easily recognized by traditional monitoring methods. Using the huge amounts of glucose data generated by CGM technology, diabetes management is expected to be more targeted, with glucose control more accurate. In this context, novel measure of glucose control represented by time in range (TIR) has been popularized, which can provide comprehensive information including hyperglycemia, hypoglycemia, and glucose fluctuation. Hence, the modern approach to glucose control should focus not only on glycosylated hemoglobin, but also pay attention to new metrics such as TIR. In the future, more mature, minimally invasive and even non-invasive glucose monitoring technologies that are comfortable, stable and highly accurate should be further developed to greatly improve the experience and enthusiasm of the patients in blood glucose monitoring. Meanwhile, closed-loop insulin infusion system should be further developed, to truly realize individualized and automated glucose control, as well as further improvement of glucose control in the patients with diabetes.

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Frontier review
Aptamer-drug conjugates (ApDCs): new trend for cancer precision therapy
HAN Yongqi, HAN Da, XIA Qian, JI Dingkun, TAN Weihong
2022, 42 (9):  1176-1181. 
doi: 10.3969/j.issn.1674-8115.2022.09.003

Abstract ( 66 )   HTML ( 186 )   PDF (1279KB) ( 86 )  

Cancer is a worldwide medical issue that seriously threatens human health. Precision molecular medicine provides a new strategy for cancer theranostics. As excellent targeting recognition molecules and drug delivery platforms, aptamers and aptamer drug-conjugates (ApDCs) have provided a series of useful molecular tools for cancer precision therapy. In this paper, the properties and the selection techniques of aptamers, the construction of ApDCs and their applications to clinical tumor-targeting therapy are reviewed. Additionally, the challenges and perspective of ApDCs in precision molecular medicine for cancers are presented. This review may provide new horizons for molecular-targeted anti-tumor drugs in the therapy of clinical malignant tumors.

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Research progress and clinical intervention strategy of age-related hearing loss
HUANG Zhiwu, WU Hao
2022, 42 (9):  1182-1187. 
doi: 10.3969/j.issn.1674-8115.2022.09.004

Abstract ( 47 )   HTML ( 25 )   PDF (1903KB) ( 72 )  

Age-related hearing loss (ARHL), also known as presbycusis, has not been paid enough attention to worldwide due to the lack of awareness of its harmfulness for a long time. In the past decade, with the increase of aging and related social problems, ARHL has attracted more and more attention from government and society, and its pathological mechanism and clinical intervention research have also developed rapidly. However, it is still unclear about the pathogenic mechanism of ARHL caused by genetic and environmental factors. This review briefly introduces the basic pathological characteristics of ARHL, and summarizes the related researches on its genetic and environmental (especially noise exposure) pathogenic mechanism and clinical intervention effect, as well as the research progress of the writers' research group in this field, which is expected to help government promote and formulate relevant interventions and medical policies on the hearing health in the elderly.

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Innovative research team achievement column
Immune inhibitory receptor LILRB2 enhances SARS-CoV-2 spike protein-mediated immune inflammation
YANG Wenqian, CHEN Chiqi, ZHAO Lu, CAO Liyuan, XIA Yiqiu, LU Zhigang, ZHENG Junke
2022, 42 (9):  1188-1196. 
doi: 10.3969/j.issn.1674-8115.2022.09.005

Abstract ( 61 )   HTML ( 28 )   PDF (2295KB) ( 93 )  

Objective ·To explore the possible roles of immune inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) in the immune inflammation after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and provide a potential therapeutic way for the coronavirus disease 2019 (COVID-19). Methods ·The supernatants containing the extracellular domain of spike protein (S-ECD) were collected, and the detection of the protein expression and activity in the conditional medium by Western blotting and flow cytometric analysis was followed by. The binding of S-ECD with LILRB2 was measured by co-immunoprecipitation and flow cytometric analysis. The mRNA expression levels of several inflammation genes in a human mononuclear cell line (THP1) or peripheral blood mononuclear cells (PBMC) were measured after spike protein stimulation for 24 h by quantitative RT-PCR. The protein levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the conditional medium were examined by enzyme-linked immunosorbent assay (ELISA). The siLILRB2 was transferred into CD33+ myeloid cells purified from human peripheral blood with Lipofectamine 3000 reagents. The knockdown efficiency was detected 24 h after transfection by flow cytometric analysis. The difference in the protein levels of IL-6 between the control cells and LILRB2-knocked-down cells after spike protein treatment was evaluated by ELISA. Results ·The study established a transfection system with 293T cells by which the SARS-CoV-2 S-ECD could be secreted to supernatants with normal biological activities. The interaction and the binding of spike protein with LILRB2 were evaluated by a co-immunoprecipitation assay and flow cytometric analysis, respectively. The mRNA expression levels of IL-6, IL-8, arginase 1 and IL-2 in THP1 cells were significantly up-regulated 24 h after spike protein treatment compared to the control cells (all P<0.05). Consistently, the mRNA levels of IL-6, transforming growth factor-β(TGF-β), IL-8, IL-10 and IL-1β in PBMC were notably increased after spike protein stimulation (all P<0.05). In addition, spike protein could also induce the release of IL-6 and IL-1β in PBMC as measured by ELISA (all P<0.05). More importantly, spike protein was able to increase the secretion of IL-1β and IL-6 by CD33+ myeloid cells 24 h after treatment (both P<0.05). LILRB2-overexpressing THP1 cells produced more IL-6 24 h after treatment with spike protein than the control cells (P<0.05). Two siRNAs could efficiently down-regulate the expression of LILRB2 in CD33+ cells as evaluated by flow cytometric analysis. Consistently, spike protein had no effect on the IL-6 secretion to supernatant from LILRB2-knockdown CD33+ myeloid cells. Conclusion ·SARS-CoV-2 can induce cytokine release syndrome by inflammatory factors, such as IL-6 and IL-1β, released by myeloid cells through spike protein binding to LILRB2.

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Transcriptomic analysis of metabolic characteristics of the immune cells in systemic lupus erythematosus patients
HAN Xiaxia, JIANG Yang, GU Shuangshuang, DAI Dai, SHEN Nan
2022, 42 (9):  1197-1207. 
doi: 10.3969/j.issn.1674-8115.2022.09.006

Abstract ( 48 )   HTML ( 28 )   PDF (10727KB) ( 32 )  

Objective ·To study the metabolic pathway activity level of the immune cell subsets in the patients with systemic lupus erythematosus (SLE) by bioinformatics analysis. Methods ·The matrix expression data of PBMCs collected from SLE patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) Datasets, as well as the transcriptome data of T cell and B cell subsets from SLE patients and healthy controls. The differentially-expressed genes (DEGs) were identified in the standardized sequence data. Pathway enrichment analysis of DEGs was performed by online Enrichr tools, and the common up-regulated pathways were determined by comparative analysis. Gene set enrichment analysis (GSEA) was used to identify pathways that were enriched in the experiment processed with the whole gene expression matrix. RNA-seq data from PBMCs samples of SLE patients and healthy controls were used to characterize the immune cell composition. The targeted pathway was annotated with gene expression. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) technique was performed to detect the chromatin accessibility of glycolysis-related genes in SLE patients and healthy controls. Results ·① Venn diagram depicted 139 common upregulated pathways in GSE169080, GSE144390 and GSE139350 data sets, and GSEA results showed that multiple classical metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), were up-regulated in SLE patients. ② Immune cell composition analysis of PBMCs showed that the proportions of T cells, B cells and NK cells were higher in SLE patients, and the expression of genes encoding multiple enzymes of metabolic pathway in T cells and B cells were higher than those in healthy controls. ③ Compared to healthy controls, the intensity of ATAC-seq signal was significantly enhanced at transcriptional regulatory sites of SLC2A3, PKM and LDHA in peripheral B cells from SLE patients. ④ GSEA results and visualization analysis of metabolic pathways of SLE B cell subsets showed that the memory B cells and plasmablasts displayed a higher metabolic state than na?ve B cells. Conclusion ·Multiple metabolic pathways are altered in SLE patients and the metabolic level of effector B cells is higher than na?ve B cells in SLE patients.

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Renewal of esophageal and gastric macrophages by circulating monocytes
ZHU Yiwen, YU Qing, WU Xinrui, LU Jie, CHEN Zihao, GINHOUX Florent, SU Bing, LIU Zhaoyuan
2022, 42 (9):  1208-1215. 
doi: 10.3969/j.issn.1674-8115.2022.09.007

Abstract ( 63 )   HTML ( 27 )   PDF (9091KB) ( 22 )  

Objective ·To reveal the renewal kinetics of esophageal and gastric macrophages by circulating monocytes. Methods ·The monocytes of the Ms4a3Cre -RosaTdT fate mapping model mice carry an irreversible tdTomato red fluorescent marker. The macrophages derived from these monocytes will also carry red fluorescence, distinguishing them from the embryonic-derived macrophages. The contribution of monocytes to esophageal and gastric macrophages was determined by detecting the number and the proportion of red fluorescence labeling in the ionized calcium-binding adapter molecule 1 (IBA1) positive macrophages in the esophagus and stomach from Ms4a3Cre -RosaTdT mice of different ages (2 weeks, 8 weeks and 15 months of age) by immunofluorescence imaging. Results ·In the esophagus and stomach of 2-week-old Ms4a3Cre -RosaTdT mice, most macrophages were tdTomato negative, indicating that the esophageal macrophages and gastric macrophages of young mice were mainly embryonic derived. In 8-week-old adult mice, many tdTomato positive monocyte-derived macrophages could be detected in the stomach. In 15-month-old mice, most of the esophageal and gastric macrophages were tdTomato positive, indicating that the esophagus and stomach macrophages of the old mice were mainly produced by monocytes. Conclusion ·In juvenile mice, esophageal and gastric macrophages are mainly embryonic-derived macrophages, while with age, monocyte-derived macrophages gradually replace tissue-resident macrophages in the esophagus and stomach. Esophageal and gastric macrophages in aged mice are mainly derived from circulating monocytes. Thus, the macrophage pool in the esophagus and stomach of mice consists of embryonic- and mononuclear-derived cells with their proportions changing with age.

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Anatomical structure of laminar specific subtypes of medial prefrontal cortex-basolateral amygdala projection neurons
HE Luyao, HUANG Dongping, SHAO Mengmeng, ZHANG Kai, REN Baihui, KONG Qingdan, XU Tianle, LÜ Jiangteng
2022, 42 (9):  1216-1224. 
doi: 10.3969/j.issn.1674-8115.2022.09.008

Abstract ( 42 )   HTML ( 25 )   PDF (6460KB) ( 8 )  

Objective ·To dissect the fine anatomical structure of medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) projection neurons based on regional and laminar specificity in the cortex in mice. Methods ·The retrograde tracer of adeno-associated viral (AAV) vectors were injected into BLA of C57BL/6 mice. Twenty-one days after the injection, the mice were sacrificed and the brains were harvested. The coronal sections containing mPFC were prepared by using a cryostat microtome. The images were taken by fluorescence microscopy. Then the representative brain slices containing mPFC were selected and the distribution of virus-labeled cell bodies in different subregions of mPFC was analyzed. By using transgenic mouse lines (Tbr2-CreER::LSL-Flp mice and Rbp4-Cre mice)with Flp- or Cre-dependent AAV, layer 2 (L2) and layer 5 (L5) projection neurons in mPFC and their axons in BLA were marked, respectively. Twenty-eight days after the injection, the mice were sacrificed and the brains were also harvested. Coronal sections of the BLA were collected. The brain slices were imaged by fluorescence microscopy after immunofluorescence staining. By measuring the fluorescence intensity of projecting axons in different regions within BLA, the spatial distributions of the axons in BLA of mPFC L2 and L5 projection neurons were compared. Results ·Through fluorescence microscopy and quantitative analysis, it was found that the cell bodies of BLA projection neurons were mainly located at L2 and L5 in the dorsal mPFC (dmPFC) which contains anterior cingulate cortex and prelimbic cortex. However, the distribution of BLA projection neurons in the ventral mPFC (vmPFC) including medial orbital cortex and infralimbic cortex did not exhibit the similar distribution. When studying the axonal distribution of dmPFC projection neurons in two layers, it was found that the axons of L2 projection neurons dispersed in the BLA, while the axons of L5 projection neurons were mainly located in the dorsal region of BLA. Conclusion ·The cell body distribution of mPFC-BLA projection neurons shows regional specificity and laminar specificity. The axon projections initiated from different layers of dmPFC also exhibit regional specificity in BLA.

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Role of human pleiotrophin in the metastasis of malignant peripheral nerve sheath tumor
CUI Xiwei, CHUNG Manhon, AIMAIER Rehanguli, WANG Zhichao, LI Qingfeng
2022, 42 (9):  1225-1238. 
doi: 10.3969/j.issn.1674-8115.2022.09.009

Abstract ( 39 )   HTML ( 27 )   PDF (11396KB) ( 10 )  

Objective ·To investigate the role of pleiotrophin (PTN) in the proliferation, migration and invasion of malignant peripheral nerve sheath tumor (MPNST). Methods ·The expression of PTN was verified by immunochemistry and bioinformatics analysis. By lentivirus transfection, the PTN-overexpressing and the PTN-knocked-down MPNST cell lines were established. To validate the role of PTN in MPNST migration and invasion, cell wound healing assay and Transwell migration/invasion assays were performed in boththe PTN-overexpressing MPNST cells and the PTN-knocked-down cells. By CCK8 assay, EdU assay and colony formation assay, the effects of PTN on the proliferation and the colony formation capabilities were evaluated. The pathway expression pattern regulated by PTN was validated by Western blotting and high-throughput transcriptome sequencing. To identify the biological function of PTN in vivo, an MPNST lung metastatic model in Balb/c nude mice was established. By mouse tail intravenous injection technique, PTN-knocked-down MPNST cells (experimental group) and negative control cells (control group) were injected into Balb/c nude mice, respectively. Results ·According to the immunochemistry staining results of the MPNST tissue samples from 49 patients and the normal nerve tissue samples from 3 non-MPNST people, PTN was significantly down-regulated in the MPNST tissues. In cell wound healing assay and Transwell migration/invasion assay, knocking down PTN significantly enhanced the migration and invasion capabilities of MPNST cells, while PTN overexpression inhibited them. The results of CCK8 assay, EdU assay and colony formation assay indicated that PTN overexpression hindered the proliferation of MPNST cells while colony formation was barely impacted; no significant differences in these assays were detected in the PTN-knocked-down cells. According to Western blotting assay, PTN overexpression activated mitogen activated protein kinase (MAPK) pathway while knocking down PTN showed mild influence. Transcriptome high-throughput sequencing showed that the expression levels of the genes related with programmed cell death pathway changed in the PTN-overexpressing cells. In the in vivo experiments, there was no significant difference in the tumor formation rate; however, the quantity and the volume of lung metastasis lesions were both larger in the experimental group. The most mice in the experimental group were diagnosed with severe pulmonary interstitial disease, and their growth rate of body mass also decreased. Conclusion ·PTN is down-regulated in the MPNST tissue and overexpressing PTN inhibites proliferation, migration and invasion of the MPNST cells in vitro. The ability of PTN-knocked-down MPNST cells to metastasize to the lungs in mice is enhanced.

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Adaptation and adaptability investigation of Improving Parents as Communication Teachers (ImPACT) program for autism spectrum disorder
WU Danping, REN Fang, SHEN Lixiao, XUE Minbo, WANG Junli, LI Fei, XU Mingyu
2022, 42 (9):  1239-1246. 
doi: 10.3969/j.issn.1674-8115.2022.09.010

Abstract ( 52 )   HTML ( 31 )   PDF (2133KB) ( 15 )  

Objective ·To adapt and investigate the adaptability of the parent-mediated intervention program “Improving Parents as Communication Teachers (ImPACT)” for autism spectrum disorder (ASD) under the background of Chinese culture. Methods ·There were 4 procedures of adaptation: information gathering, preliminary adaptation design, preliminary adaptation test, and adaptation refinement. In the information collection part, 8 experts (6 pediatrics and 2 psychotherapists) were invited to have 6 focus group discussions, and preliminary adaptation was made in the aspects of language, intervention form, program structure, cultural customs, etc., according to expert suggestions. Then 16 ASD parents were recruited to participate in the ImPACT program after the preliminary adaptation. Adaptative investigation of ImPACT was carried out simultaneously in the preliminary adaptation test stage. Results ·The adaptability investigation results of preliminary adaptation program showed that all parents believed that “the pace of the program was well controlled, and they could follow the rhythm of the therapist to complete the learning of skills”. Among these parents, 66.67% believed that “the course was fully prepared, the explanation was clear, and the goal was clear”, and 33.34% believed that “rich examples were provided to help understand intervention skills” in the learning process. As for the feedback of skill practice homework after each session, 83.33% of parents believed that “homework could be easily completed, and help them better learn intervention skills”, and all parents believed that “comments were timely, and the content of comments could help them answer questions and solve doubts”. The difficulties in mastering, i.e., the 7th session (shaping the interaction), the 6th session (teaching new imitation and play skills), and the 5th session (teaching new communication skills) were further adjusted after discussion with the expert group to make the final plan more convenient for parents to master. Conclusion ·After adaptation and adaptability investigation, a parent-mediated intervention program ImPACT which is more suitable for the families of ASD children in China has been formed.

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Basic research
TCF3 knockdown inhibits the decidualization of human endometrial stromal cells
WEI Xiaowei, TIAN Fuju, LIU Xiaorui, ZENG Weihong, CHEN Cailian, LIN Yi
2022, 42 (9):  1247-1257. 
doi: 10.3969/j.issn.1674-8115.2022.09.011

Abstract ( 52 )   HTML ( 34 )   PDF (5456KB) ( 17 )  

Objective ·To investigate the effect of transcription factor 3 (TCF3) on decidualization of human endometrial stromal cells (HESCs). Methods ·HESC decidualization in vitro was induced by 8-bromoadenosine 3',5'-cyclic adenosine monophosphate (8-Br-cAMP) and medroxy progesterone acetate (MPA). Small interfering RNA (siRNA) against TCF3 was used to construct TCF3-knockdown cell model. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to confirm the knockdown efficiency of TCF3. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of decidual markers, including insulin like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The morphological changes of HESCs after decidualization and after TCF3 knockdown were detected by Alexa Fluor-labeled phalloidin staining. The HESCs were divided into three groups: non-decidualized+NC (transfected with control siRNA) group, decidualized 4 d+NC group, and decidualized 4 d+siTCF3 (transfected with TCF3 siRNA) group, and RNA sequencing was performed. In order to explore the mechanism of TCF3 regulating the decidualization of HESCs, cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted in the three groups of cells. qPCR was used to confirm the results of RNA sequencing analysis. Results ·The expression level of TCF3 increased gradually after 2 d and 4 d of decidualization of HESCs. Both ELISA and RT-qPCR results showed that after decidualization for 2 d or 4 d, the expression of decidual markers IGFBP1 and PRL decreased after TCF3 knockdown. Phalloidin staining results showed that after decidualization, the cell morphology changed from a long and slender fusiform structure to a large and round cell shape, while after TCF3 was knockdown, the cell morphology returned to the long fusiform structure. RNA sequencing analysis showed that the differential genes were mainly enriched in the cytokine-cytokine receptor pathway, which was further verified by GSEA analysis. RT-qPCR results confirmed that knockdown of TCF3 down-regulated the expression of several cytokines, such as leukemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 1 β (IL1B), interleukin 1 receptor type 1 (IL1R1), and interleukin 1 receptor type 1 (CSF1). Conclusion ·Down-regulation of TCF3 in HESCs inhibits decidualization maybe through regulating the expression of cytokines IL-6, IL1B, IL1R1 and CSF1.

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Exploring potential new receptors for ELABELA in human embryonic stem cells by Crispr/Cas9-mediated gene editing system
ZHOU Yue, CHENG Chen, ZHENG Enlin, MENG Zhuo, WANG Jian, WANG Qingjie, HE Yongning, SUN Kun
2022, 42 (9):  1258-1264. 
doi: 10.3969/j.issn.1674-8115.2022.09.012

Abstract ( 50 )   HTML ( 32 )   PDF (5770KB) ( 23 )  

Objective To verify the existence of potential new receptor of ELABELA (ELA) in human embryonic stem cells (hESC) by Crispr/Cas9-mediated gene editing system. Methods The dynamic expression levels of ELA and its receptor APJ were examined by collecting cells at different days (0?13 d) during the directed differentiation of stem cells into cardiomyocytes. The mRNA expression levels of cardiomyocyte markers MYH6, TnnT2 and NKX2.5 were observed by adding the APJ inhibitor ML221 during the directed differentiation of stem cells to cardiomyocytes. Human embryonic kidney suspension cells (HEK-293F) were used to express recombinant ELA green fluorescent protein (GFP). To verify whether ELA binds through its C-terminus or N-terminus, two recombinant plasmids with GFP sequences which were inserted into the C-terminus or the N-terminus of ELA-32 sequence were constructed. The only known receptor for ELA, APJ-knockout hESC, was constructed and validated by using Crispr/Cas 9 gene editing technology. Two GFP-ELA recombinant proteins were added exogenously to the successfully constructed knockout cell lines and normal cell lines, and the ability of ELA to enter the cells was observed by fluorescence microscopy. Results During the stem cell period, ELA was highly expressed while APJ was basically not expressed; the peak of ELA expression was at the 6th day of differentiation while the peak of APJ expression appeared at the 3rd day of differentiation. The efficiency of stem cell directed differentiation to cardiomyocytes was not affected by exogenous addition of the APJ inhibitor ML221 (P>0.05). After DNA sequencing and Western blotting validation, the APJ-knockdown stem cell line was successfully constructed. When APJ was knocked down, exogenous addition of ELA N-terminal fluorescent protein was still able to enter the cells, while the absence of fluorescence of ELA C-terminal fluorescent protein indicated that ELA C-terminal fluorescent protein could not enter the cells. Conclusion There are other ELA receptors in hESCs that are not APJ. Otherwise, the binding sites of ELA and its receptor are mainly located at the C-terminal of ELA.

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Effect of α-mangostin on amyotrophic lateral sclerosis and its mechanism
WANG Dayuan, XU Jianrong, JIANG Gan, SONG Qingxiang, CHEN Jun, SONG Huahua, GU Xiao, GAO Xiaoling
2022, 42 (9):  1265-1274. 
doi: 10.3969/j.issn.1674-8115.2022.09.013

Abstract ( 39 )   HTML ( 34 )   PDF (5271KB) ( 24 )  

Objective ·To study the effect of α-mangostin (AM) on the superoxide dismutase 1 (SOD1) mutant amyotrophic lateral sclerosis (ALS) and the possible mechanism. Methods ·The ATP level in the microglia was measured by kits to investigate the effect of AM on the energy balance in the SOD1 aggregates-treated microglia (SOD1-ALS model microglia). Western blotting was used to detect the activation levels of AMP-activated protein kinase (AMPK) and the key molecules in its metabolic regulation pathway including liver kinase B1 and PPARγ coactivator 1α, in order to explore the regulatory role of AM on AMPK pathway in the disease-associated microglia. The ATP level was also detected after AMPK activation being inhibited by compound C to explore the role of AMPK in the regulation of energy balance by AM in the SOD1-ALS microglia. The microglial uptake and degradation of SOD1 aggregates was detected by using ELISA with or without inhibition of AMPK activation, to explore the role of AMPK-mediated energy regulation in AM regulating SOD1 clearance in the disease-associated microglia. Western blotting and immunofluorescence were used to study the effect of AM on microglial autophagy and the role of autophagy in AM regulating the degradation of SOD1 in the microglia. AM-encapsulated nanoparticles (NPAMs) were prepared to realize the in vivo treatment of AM. NPAMs were injected into the SOD1*G93A ALS model mice through the caudal vein for 30 d, once a day. SOD1 aggregates were detected by immunohistochemistry in the lumbar spinal cords of the ALS mice. Neuronal damage and loss were measured by using Nissl staining and anti-NeuN immunohistochemistry. Motor ability of the ALS mice was evaluated by rotarod test and hindlimb clasping test. Disease progress of the ALS mice was evaluated by recording body mass and survival time. Results ·AM increased the ATP level in the diseased-associated microglia and enhanced microglial phagocytosis and autophagy-mediated degradation of SOD1 aggregates. While inhibiting AMPK pathway abolished these effects of AM, NPAM reduced SOD1 aggregates in the lumbar spinal cord of the SOD1*G93A ALS model mice, and reduced the neuron damage and loss. NPAM also alleviated the body mass loss and the damaged motor ability of the ALS mice. Conclusion ·AM enhances microglial clearance of SOD1 aggregates through AMPK-mediated recovery of energy balance, and thus alleviates the neuropathological changes and symptoms in ALS mice.

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Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice
LI Lu, LI Yulin, LIU Yan, DUAN Shengzhong
2022, 42 (9):  1275-1287. 
doi: 10.3969/j.issn.1674-8115.2022.09.014

Abstract ( 45 )   HTML ( 31 )   PDF (7880KB) ( 12 )  

Objective ·To study the effects of periodontitis (PD) on transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice and explore the mechanisms. Methods ·Twenty-five C57BL/6J mice were randomly divided into Sham operation (Sham) group, transverse aortic constriction (TAC) group, and periodontitis combined with TAC (TAC+PD) group. PD was induced by ligation of mouse molars and application of subgingival plaques of PD patients. TAC surgery was performed after the establishment of PD model. Cardiac function was assessed by echocardiography at 4 weeks after Sham or TAC surgery. The mice were then sacrificed and the samples were collected for quantitative realtime PCR (qRT-PCR), immunohistochemistry, immunofluorescence, and 16S rRNA gene sequencing. Results ·The mice in the TAC+PD group manifested significantly more resorption of the alveolar bone and higher expression of inflammatory genes in gingiva compared to Sham and TAC groups, demonstrating successful establishment of PD models in TAC mice. Compared to those in the TAC group, the mice in the TAC+PD group had significantly lower left ventricular ejection fraction (EF) and left ventricular shortening fraction (FS), illustrating that PD exacerbated TAC-induced cardiac dysfunction. Compared to those in the TAC group, the mice in the TAC+PD group had significantly bigger heart weight to body weight ratio (HW/BW) and heart weight to tibia length ratio (HW/TL), lung weight to body weight ratio (LW/BW), and cross-sectional area of cardiomyocytes, as well as higher expression of hypertrophy-related genes, demonstrating that PD exacerbated TAC-induced cardiac hypertrophy and heart failure. Compared to those in the TAC group, the mice in the TAC+PD group had significantly larger fibrotic areas and higher expression of fibrosis-related genes in the heart, bigger spleen weight to tibia length ratio (SW/TL) and higher expression of inflammatory genes in the heart, illustrating that PD exacerbated TAC-induced cardiac fibrosis and inflammation. Results of 16S rRNA gene sequencing showed that relative abundances of Streptococcus and Veillonella were significantly increased in the oral ligatures of mice in the TAC+PD group compared to the TAC group. Relative abundances of Ralstonia, and Pelomonas were significantly increased in the hearts of mice in the TAC+PD group. Comparison of oral microbiota and heart microbiota of the mice in the TAC+PD group revealed that relative abundances of Ralstonia and Pelomonas in hearts were significantly higher than those in oral ligatures. Conclusion ·PD aggravates TAC-induced cardiac dysfunction, cardiac hypertrophy, fibrosis, and inflammation in mice. The mechanisms may be related to alterations in oral microbiota, particularly bacterial genera including Ralstonia and Pelomonas.

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Screening of MUCIN family members synergistic with MUC1 in tumor chemoresistance
TANG Kairan, WU Qiong, HUANG Sijia, QIU Xudong, LI Wenyan, DENG Huayun, HUANG Lei
2022, 42 (9):  1288-1295. 
doi: 10.3969/j.issn.1674-8115.2022.09.015

Abstract ( 34 )   HTML ( 34 )   PDF (2318KB) ( 9 )  

Objective ·To screen partners of mucin 1 (MUC1) in MUCIN family members that involve in chemoresistance. Methods ·Two pairs of cell lines were employed, including HeLa229/TR-CasCTL and HeLa229/TR-CasMUC1, and HeLa229/P and paclitaxel-resistant cell HeLa229/TR. Firstly, the cells were employed to detect the mRNA levels of MUCINs by quantitative real-time PCR (qPCR). The correlation of mRNA levels between MUC1 and MUCINs was analyzed. Then, Western blotting was performed to detect the protein levels of the selected MUCINs to get the proteins correlated with MUC1 at both mRNA and protein levels. IC50 assay was further employed to detect the role of target protein in paclitaxel resistance by knockdown of the gene through shRNA in HeLa229/TR cells. The mean expression levels of MUC1 and MUC13 in a variety of cancer tissues were further explored in the GEPIA database. The R2 database was further employed to detect the linear correlation of the expression between MUC1 and MUC13 in cervical, colon and pancreatic cancer tissues. Finally, the expression of MUC1 and MUC13 was analyzed by the Kaplan-Meier Plotter database in relation to the survival rate of patients with gastric cancer. Results ·The detection of qPCR showed that MUC13 and MUC18 exhibited correlation with MUC1 at the mRNA level in MUCIN family members. Western blotting showed that only MUC13 protein was up-regulated with the up-regulation of MUC1, while down-regulated with the silence of MUC1. IC50 assay displayed that silencing of MUC13 in HeLa229/TR decreased IC50 to paclitaxel. By searching the GEPIA database, the expression levels of MUC1 and MUC13 were simultaneous high or low in a variety of cancer tissues. From the R2 database, MUC1 and MUC13 showed a positive linear correlation in cervical, colon and pancreatic cancer tissues. In addition, the negative relationship of the expression of MUC1 and MUC13 and survival rate of patients with gastric cancer from the Kaplan-Meier Plotter database was observed. Conclusion ·MUC13 is a partner for MUC1 in promoting tumor chemoresistance. The expression levels of MUC1 and MUC13 are negatively related with the survival rate of cancer patients. It's feasible for joint inhibiting MUC1 and MUC13 to overcome chemoresistance.

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Clinical research
Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG
YANG lin, WANG Jingbo, HUANG Xiaojuan, REN Jiliang, YUAN ying, TAO Xiaofeng
2022, 42 (9):  1296-1302. 
doi: 10.3969/j.issn.1674-8115.2022.09.016

Abstract ( 49 )   HTML ( 33 )   PDF (2073KB) ( 29 )  

Objective ·To explore the feasibility of intraoperative real-time fluorescence imaging in the diagnosis of oral cancer cervical lymph node metastasis and extra-nodal extension (ENE) in the patients with oral squamous cell carcinoma (OSCC) by using the surface-smeared fluorescent probe cellular-mesenchymal epithelial transition factor (c-Met)?binding peptide (cMBP)? indocyanine green (ICG). Methods ·The five patients with primary OSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were selected as the research subjects. The fluorescent probe cMBP-ICG was prepared, and real-time fluorescence imaging was performed by surface smear method on the suspicious lymph nodes of the enrolled patients who underwent neck lymph node dissection. The clinical information, the pathological results and the fluorescence intensity (FI) values of lymph node real-time fluorescence imaging were collected and sorted, and lymph node metastasis and ENE were predicted according to the FIs of cMBP-ICG real-time fluorescence imaging. Results ·Intraoperative cMBP-ICG real-time fluorescence imaging of suspicious lymph nodes were performed, and imaging results of different FIs were obtained in real time. The results of 49 suspicious lymph nodes in the 5 patients showed that the sensitivity of cMBP-ICG in predicting lymph node metastasis was 100%, the specificity was 84%, the positive predictive value was 67%, and the negative predictive value was 100%. The sensitivity of cMBP-ICG in predicting lymph node ENE was 100%, the specificity was 93%, the positive predictive value was 63%, and the negative predictive value was 100%. Conclusion ·Intraoperative cMBP-ICG real-time fluorescence imaging can effectively identify lymph node metastatic and ENE in OSCC, which can provide an auxiliary method for intraoperative diagnosis of lymph node metastasis and ENE.

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Rasch analysis of postoperative cardiac rehabilitation and related factors in 3-6-year-old children with congenital heart disease
LUO Wenyi, CHEN Lin, YUAN Li, NI Ping, CAI Xiaoman, ZHANG Yaqing
2022, 42 (9):  1303-1310. 
doi: 10.3969/j.issn.1674-8115.2022.09.017

Abstract ( 46 )   HTML ( 34 )   PDF (1400KB) ( 17 )  

Objective ·To analyze the occurrence of heart failure (HF) and related functional impairment items in 3?6-year-old children with congenital heart disease (CHD) in the first year after operation by using the Rasch model. Methods ·The children aged 3?6 years old who were followed up at Shanghai Children 's Medical Center, Shanghai Jiao Tong University School of Medicine, from February to August 2021 were included. The general information of children, the evaluation of International Classification of Functioning, Disability, and Health for Children and Youth core set for children with congenital heart disease after surgery (ICF-CY-CHDS) filled by their parents and the diagnosis of HF were collected. The analysis with Rasch model was carried out by using Winsteps 3.72.3 software, and the degree of postoperative functional impairment and the difficulty of the items of the ICF-CY-CHDS were transformed into the same evaluation system (Logit value) for comparison. Multivariate Logistic regression was used to analyze the items related to HF. Results ·A total of 340 CHD children after surgery were included. The average age of the children was (4.48±1.05) years old and their average follow-up time was (8.33±2.79) months after CHD surgery. According to the analysis of Rasch model, the overall difficulty of the items of the ICF-CY-CHDS was moderate (the Logit value was 0), which was suitable for the study population. The Logit value of the overall functional impairment of 340 children was -2.35±0.87, indicating that the overall rehabilitation level of the children after CHD surgery in the first year was good; Among them, 24 children (7.1%) had HF, and the overall functional impairment of the children with HF was significantly more serious than that of the children without HF ( P=0.000). After transforming the degree of postoperative functional impairment and the difficulty of the items of the ICF-CY-CHDS into the same evaluation system, it was found that the proportions of the children failing to reach the standards in 9 items were higher in the HF children than those in the non-HF ones. The 9 items were “b1302 appetite” ( P=0.014), “b152 emotional functions” ( P=0.014), “b435 immunological system functions” ( P=0.000), “b455 exercise tolerance functions” ( P=0.014), “b530 weight maintenance functions” ( P=0.000), “b560 growth maintenance function” ( P=0.000), “d160 focusing attention” ( P=0.001), “e450 individual attitudes of health professionals” ( P=0.001), and “e580 health services, systems and policies” ( P=0.000). The results of multivariate Logistic regression demonstrated that “e580 health services, systems and policies” was the item related to HF ( OR=13.250, 95% CI 4.905?35.795). Conclusion ·The overall rehabilitation level of the children with CHD in the first year after surgery is good, but there are still a few children with HF. Making corresponding health service strategies about children 's psychological behavior, cardiopulmonary function, nutritional status, and medical environment may be helpful to improve children 's postoperative cardiac rehabilitation level and reduce the occurrence of HF.

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Observation on early microvascular changes in macular area of the fundus in children with type 1 diabetes mellitus
LI Wen, LI Yuan, YE Haiyun, ZHANG Xiaoxiao, QIAO Tong, LI Pin
2022, 42 (9):  1311-1314. 
doi: 10.3969/j.issn.1674-8115.2022.09.018

Abstract ( 40 )   HTML ( 29 )   PDF (2232KB) ( 14 )  

Objective ·To observe the changes of vascular morphology and blood flow in the macular area of the fundus of type 1 diabetic children without retinopathy by optical coherence tomography angiography (OCTA), and explore the application of OCTA in these children. Methods ·From June 2019 to February 2020, 27 type 1 diabetic children without retinopathy (54 eyes, observation group) who were hospitalized in the Department of Endocrinology of Shanghai Children′s Hospital, Shanghai Jiao Tong University School of Medicine, and 25 age-matched healthy children (50 eyes, control group) were selected. The macular area of the fundus of the two groups of children was scanned with OCTA in the range of 3 mm×3 mm and 6 mm×6 mm, respectively, and the morphology of the macular arch ring was observed. The area of foveal avascular zone (FAZ), and the vascular density and perfusion density of different zones around the foveal were quantitatively analyzed Results ·The morphology of the macular arch ring in the observation group was regular, and the FAZ area of macular area was larger than that in the control group (P=0.000). The superficial retinal vascular density and perfusion density within the diameter of 1 mm around the macular fovea were lower than those in the control group (P=0.009, P=0.012). In the observation group, the superficial retinal vascular density and perfusion density in the area outside 1 mm diameter and within 3 mm diameter around the macular fovea were (18.29±0.96) mm-1 and 0.43±0.03, while the superficial retinal vascular density and perfusion density in the area outside 3 mm diameter and within 6 mm diameter around the macular fovea were (18.58±0.69) mm-1 and 0.46±0.02, which had no significant difference with the control group. Conclusion ·In the children with type 1 diabetes mellitus, the enlargement of macular arch and the decrease of superficial retinal vascular density and perfusion density within 1 mm diameter around macular fovea may occur before retinopathy. OCTA can be effectively applied to the early monitoring of the changes of vascular morphology and blood flow in the macular area of the fundus of diabetic children.

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Mediating effects of neuroticism and immature defense on relationship between childhood trauma and obsessive-compulsive symptoms in patients with obsessive-compulsive disorder
ZHAO Qing, GU Wenjie, WANG Zhen
2022, 42 (9):  1315-1322. 
doi: 10.3969/j.issn.1674-8115.2022.09.019

Abstract ( 43 )   HTML ( 31 )   PDF (1913KB) ( 19 )  

Objective ·To explore the characteristics of childhood trauma, personality traits and defense mechanism in the patients with obsessive-compulsive disorder (OCD), and investigate the mediating effects of personality traits and defense style on the relationship between childhood trauma and obsessive-compulsive symptoms in the OCD patients. Methods ·Totally 113 patients with OCD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders-5 (DMS-5), and 66 age- and gender-matched health controls with similar education level distribution were selected. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate the severity of obsessive-compulsive symptoms. Childhood Trauma Questionnaire (CTQ) was used to evaluate the childhood trauma experience. NEO Five-Factor Inventory (NEO-FFI) was used to measure the personality traits. Defense Style Questionnaire (DSQ) was used to evaluate the defense style. The correlations among childhood experience, obsessive-compulsive symptoms, personality traits and defense style as well as mediating role of personality traits and defense style between childhood trauma and obsessive-compulsive symptoms were analyzed. Results ·Compared with the health controls, the OCD patients showed higher scores of emotional abuse [8 (5, 25) points vs 6 (5, 22) points, P<0.05] and immature defense [(4.65±1.01) points vs (3.60±0.99) points, P<0.05]. In the OCD patients, the scores of emotional abuse (r=0.211, P<0.05) and immature defense (r=0.274, P<0.05) were positively correlated with the total scores of Y-BOCS, and the neuroticism scores of NEO-FFI were positively correlated with the total scores of Y-BOCS (r=0.468, P<0.05). The pathway analysis showed the indirect effect from emotional abuse to Y-BOCS via immature defense was 0.088 (95%CI 0.003?0.173, P<0.05). The immature defense played a completely mediated role, and indirect effect from emotional abuse to immature defense via neuroticism was 0.117 (95%CI 0.014?0.219, P<0.05). Conclusion ·Compared with healthy people, OCD patients have experienced more emotional and physical childhood trauma, and have abnormal personality traits of neuroticism, extraversion and conscientiousness. They tend to use immature defense mechanisms. The emotional abuse has an impact on immature defense via neuroticism, and finally affect the obsessive-compulsive symptoms.

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Optimized study of virtual monoenergetic images derived from a dual-layer spectral detector CT in the preoperative evaluation of pancreatic ductal adenocarcinoma
YANG Yanzhao, CHANG Rui, WANG Qingrou, ZHU Naiyi, LI Ruokun, CHAI Weimin, YAN Fuhua
2022, 42 (9):  1323-1328. 
doi: 10.3969/j.issn.1674-8115.2022.09.020

Abstract ( 46 )   HTML ( 28 )   PDF (2409KB) ( 34 )  

Objective ·To explore the optimal energy level of virtual monoenergetic images (VMIs) derived from a dual-layer spectral detector computed tomography (CT) and its application value in the preoperative evaluation of pancreatic ductal adenocarcinoma (PDAC). Methods ·From January 2019 to June 2019, the images of sixty patients who underwent pancreas dynamic enhanced scanning on a dual-layer spectral detector CT and were pathologically confirmed of PDAC in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The conventional 120 kVp polyenergetic image (PI), and 40, 50, 60, and 70 keV VMIs were generated. The CT values of lesions, normal pancreatic parenchyma, peripheral pancreatic arteries and veins, and abdominal subcutaneous fat were measured, and the contrast-to-noise ratios (CNRs) of cancer-pancreatic parenchyma (CA-P), artery-cancer (A-CA), and vein-cancer (V-CA) were calculated with the standard deviation (SD) of abdominal subcutaneous fat CT value as image noise. The differences were analyzed by using paired t test and one‐way ANOVA test. Pairwise comparisons within groups were performed by using the Bonferroni method. Subjective scores were obtained based on the lesion-pancreatic parenchyma contrast, lesion boundary definition, and the overall image quality, and compared by using Wilcoxon test and Friedman test. Results ·Among PI and all VMIs, the CNRCA-P and the subjective scores of lesion-pancreas parenchyma contrast and the lesion boundary definition in pancreatic parenchymal phase were higher than those in portal vein phase (all P=0.000). The CNRCA-P , CNRA-CA, and CNRV-CA of VMIs increased significantly as the energy level decreased from 70 keV to 40 keV, while the image noise only subtly increased (all P=0.000). The VMI40 keV had the highest CNRCA-P , CNRA-CA, and CNRV-CA with lower image noise than PI (all P=0.000). The subjective scores of VMI40 keV were not lower than PI. Conclusion ·The VMI40 keV derived from the dual-layer spectral detector CT performs a better image quality, and can significantly improve the CNRCA-P , CNRA-CA, and CNRV-CA, which can optimize the preoperative imaging and the evaluation of pancreatic ductal adenocarcinoma.

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Comparative study of different pneumoperitoneum modes on lower extremity deep venous blood flow velocity in patients undergoing laparoscopic surgery
SUN Huihua, TIAN Qiuju, WU Beiwen
2022, 42 (9):  1329-1335. 
doi: 10.3969/j.issn.1674-8115.2022.09.021

Abstract ( 38 )   HTML ( 28 )   PDF (1694KB) ( 11 )  

Objective ·To investigate the effects of stabilized pneumoperitoneum and traditional pneumoperitoneum on the blood flow velocity of the lower extremity deep veins in the patients undergoing laparoscopic surgery. Methods ·According to the convenience sampling method, a total of 60 patients undergoing laparoscopic abdominal and pelvic malignant tumor surgeries in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from April 2021 to September 2021 were selected, and the stabilized pneumoperitoneum group (n=30) and the traditional pneumoperitoneum group (n=30) were compared at T0 (before anesthesia), T1 (after anesthesia), T2 (after pneumoperitoneum stabilization), T3 (pneumoperitoneum at 60 min), T4 (pneumoperitoneum at 120 min), and T5 (after pneumoperitoneum) in blood flow velocity including peak systolic velocity (PSV) and end diastolic velocity (EDV). The activated partial thromboplastin time (APTT), prothrombin time (PT) and D‐dimer (D-D) were detected at 24 h before and after surgery. Results ·CO2 pneumoperitoneum slowed down the blood flow velocity of lower extremity deep veins. Repeated measurement ANOVA analysis showed the values of Ftime, Fgroupand Finteraction were 1 253.171, 4.905 and 13.338 (P<0.05), respectively for PSV, and 1 046.798, 21.163, and 11.090, respectively for EDV (P<0.01). There were great influences on PSV and EDV in the traditional pneumoperitoneum group. With the prolongation of pneumoperitoneum time, the difference of blood flow velocity in the stabilized pneumoperitoneum group was significantly lower than that in the traditional pneumoperitoneum group at T3, T4 and T5 time points (P<0.05). There were statistically significant differences in APTT, PT and D-D between the two groups at 24 h before and after surgery (P=0.000). There was no statistical difference in the incidence of deep vein thrombosis (DVT) between the two groups (χ2=0.215, P=1.000). Conclusion ·Stabilized pneumoperitoneum and traditional pneumoperitoneum have different effects on deep venous blood flow of lower extremities. It is recommended to use stabilized pneumoperitoneum to slow down the decrease of lower limb blood flow velocity for patients undergoing a long time laparoscopic surgery.

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Public health
Dynamic changes in gut microbiota of women with gestational diabetes mellitus and the correlation with blood glucose, blood lipid and diet
WANG Jie, WU Hui, LU Lingpeng, YANG Kefeng, ZHU Jie, ZHOU Hengyi, YAO Die, GAO Ya, FENG Yuting, LIU Yuhong, JIA Jie
2022, 42 (9):  1336-1346. 
doi: 10.3969/j.issn.1674-8115.2022.09.022

Abstract ( 56 )   HTML ( 32 )   PDF (5060KB) ( 22 )  

Objective ·To explore the changes of gut microbiota in the women with gestational diabetes mellitus (GDM) during the second to the third trimesters of pregnancy, and the correlation with dietary intake and glucose-lipid metabolism. Methods ·From June 2019 to January 2021, 78 pregnant women (30 GDM women in the GDM group and 48 healthy women in the control group) in the second trimester of pregnancy were recruited from the Department of Obstetrics and Gynecology of Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine. Demographic information and blood biochemical indicators of the two groups were collected and analyzed. A semi-quantified Food-Frequency Questionnaire (FFQ) was used to compare the dietary intake of the two groups of pregnant women. Fecal samples were collected in both groups at the second and the third trimesters of pregnancy, respectively. The characteristics and similarities of gut microbiota in both groups at the second and the third trimesters were compared by 16S rRNA high-throughput sequencing. Spearman correlation heatmap was used to analyze the relation between the abundance of gut microbiota and environmental factors (blood biochemical indicators and dietary intake components) in the pregnant women at the second trimester. Results ·Compared with the control group, the women in the GDM group gained more weight during pregnancy (P=0.012). In the second trimester, compared with the control group, the fast blood glucose level, the blood glucose level at oral glucose tolerance test (OGTT) 1 h and 2 h, and the triacylglycerol level of the pregnant women in the GDM group were higher, and the high-density lipoprotein and the low-density lipoprotein levels were lower (all P<0.05). The results of dietary intake during pregnancy showed that the fat intake level of the pregnant women in the GDM group was higher than that in the control group (P=0.046). From the second to the third trimester of pregnancy, there was no significant difference in the α-diversity and β-diversity of gut microbiota between the GDM group and the control group. The gut bacterial composition at genus level of the GDM group at the second trimester had the least similarity with that of the other three groups (GDM group at the third trimester, control group at the second trimester and the third trimester), while the GDM group and control group had the most similar gut bacterial composition at genus level in the third trimester. Spearman correlation heatmap analysis showed that the abundance of Butyricicoccaceae was positively correlated with dietary fiber and vegetable intake level (r=0.365, P=0.024; r=0.469, P=0.003), the abundance of Klebsiella was positively correlated with triacylglycerol level (r=0.329, P=0.044), and the abundance of Bifidobacterium was negatively correlated with blood glucose level at OGTT 2 h (r=-0.364, P=0.025). Conclusion ·The composition of gut microbiota of pregnant women in the GDM group and control group in the second trimester of pregnancy is significantly different from that in the third trimester of pregnancy. The disorder of gut microbiota related to GDM in the second trimester of pregnancy may be related to glucose-lipid metabolism, dietary fat and vegetable intake level.

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Techniques and methods
Experimental study on the accuracy evaluation of robot-assisted osteotomy of genioplasty
HUI Wenyu, WU Jinyang, HUANG Jianhua, LUAN Nan, ZHANG Zhiyuan, ZHANG Shilei
2022, 42 (9):  1347-1352. 
doi: 10.3969/j.issn.1674-8115.2022.09.023

Abstract ( 53 )   HTML ( 32 )   PDF (3054KB) ( 16 )  

Objective ·To preliminarily evaluate the execution accuracy of the self-developed cranial-maxilofacial robot (CMF ROBOT) system for genioplasty osteotomy of skull models. Methods ·Nine patients with chin deformity who were admitted to Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from August 2019 to October 2020 were included in the study. Before the operation, the spiral CT images of the whole head of the patients were collected, the skull models were made by 3D printing, and the virtual surgical planning was carried out. During the operation, the experimental group used CMF ROBOT system to perform automatic osteotomy on 9 skull models; the control group was manually osteotomized by senior surgeons assisted by 3D printing surgical guide plate. After the operation, spiral CT scanning was performed to measure the distance error and the direction error of the osteotomy plane of the two groups in three dimensions, and the differences of the two errors between the two groups were statistically analyzed. Results ·The osteotomy of genioplasty was successfully completed in the two groups. The distance error of the overall osteotomy in the experimental group was (1.40±0.27) mm and the direction error was 7.03°±3.02°, while the distance error of the overall osteotomy in the control group was (1.23±0.27) mm, and the direction error was 6.08°±2.24°. There was no significant difference between the two errors mentioned above (P=0.256, P=0.462). Conclusion ·The CMF ROBOT system can complete the automatic osteotomy of genioplasty according to the preoperative planning, and the distance error and direction error of the osteotomy surface can reach the precision level of manual osteotomy assisted by 3D printing surgical guide plate.

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Accuracy of dental implant placement in fully edentulous patients using a dynamic navigation system
TAO Baoxin, LAN Kengliang, HUANG Wei, WANG Feng, SHEN Yihan, WU Yiqun
2022, 42 (9):  1353-1360. 
doi: 10.3969/j.issn.1674-8115.2022.09.024

Abstract ( 35 )   HTML ( 36 )   PDF (3796KB) ( 16 )  

Objective ·To study the accuracy of dental implant placement in fully edentulous patients using a dynamic navigation system. Methods ·Nine fully edentulous patients [8 males and 1 female with the mean age of (48.78±15.25) years old], including 5 maxillae and 4 mandibles, from December 2020 to January 2022, in the Department of Second Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were included, where 56 implants were placed by a dynamic navigation system and 1 was by freehand. The preoperative plans and the postoperative cone-beam CT were fused, and the entry deviation, exit deviation and angle deviation between the planned and placed dental implants were measured and recorded. According to different jaws, the implants were divided into maxilla and mandible group, and the implants were split into left and right group according to their locations to the midline. The dental implants were classified into anterior and posterior group based on the placed location. The differences of the three deviations between different groups were analyzed by using approximate t test and Mann-Whitney U test. Results ·The median (lower quartile, upper quartile) of entry deviation, exit deviation and angle deviation of dental implants were 1.06 (0.54, 1.54) mm, 1.11 (0.51, 1.56) mm and 3.33° (1.77°, 4.52°), respectively. No significant difference was found in the three deviations, irrespective of the different jaws (maxilla and mandible) (P>0.05) and implant locations (left and right side) (P>0.05). The angle deviation of the anterior implants was significantly higher than that of the posterior implants (P=0.029), but the entry deviation and exit deviation showed no significant difference between the anterior and posterior group (P>0.05). Conclusion ·The dynamic navigation system can achieve acceptable accuracy of dental implant placement in the fully edentulous patients.

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